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| Diagram of conserved motifs among DEAD box RNA helicase family proteins. |
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Description | DDX1 protein is a putative RNA helicase containing the characteristic Asp-Glu-Ala-Asp (DEAD) conserved sequence motif (Linder et al., 1989). It is composed of 740 amino acid residues (82432 Da). Proteins of this family (more than 30 from bacteria to humans) have been described to be implicated in a number of cellular processes involving alteration of RNA secondary structure such as translational initiation, nuclear and mitochondrial RNA splicing, and ribosome/spliceosome assembly (Rocak and Linder, 2004). |
Expression | DDX1 mRNA is widely expressed in many tissues, but its expression level is highest in testis (Tanaka et al., 2009). DDX1 level tends to be higher in tumor-derived cells than in normal tissues. |
Localisation | DDX1 protein is localized both in the cytoplasm and nucleus of DDX1 gene-amplified neuroblastoma and retinoblastoma cell lines, but mainly located in the nucleus of normal fibroblasts (Godbout et al., 1998). |
Function | DDX1 is believed to regulate translational initiation, nuclear hnRNA splicing, ribosome/spliceosome assembly, and mRNA synthesis as a putative ATP-dependent RNA helicase. DDX1 is associated with a pre-mRNA 3'-end cleavage protein CstF-64 (Bleoo et al., 2001) and heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Chen et al., 2002). hnRNP-K is involved in cell migration and cytoplasmic accumulation of hnRNP-K is crucial for metastasis (Inoue et al., 2007). It was reported that DDX1 interacts with nuclear diffusion inhibitory signal (NIS) motif of HIV-1 Rev protein in human astrocytes. Accumulation of DDX1 in astrocytes changed sub-cellular distribution of Rev from nuclear to cytoplasmic (Fang et al., 2005). More recently, it was reported that DDX1 is recruited to the sites of DNA double strand breaks in cells exposed to ionizing radiation and removes single stranded RNAs to facilitate the repair reaction of transcriptionally active regions of the genome (Li et al., 2008). In retinoblastoma and neuroblastoma cell lines, co-amplification of DDX1 and the proto-oncogene MYCN has been demonstrated (Godbout and Squire, 1993; Godbout et al., 1998). Similar gene amplification of the genomic region containing DDX1 and MYCN was observed in alveolar rhabdomyosarcoma samples (Barr et al., 2009) and Wilms tumor-derived cells (Noguera et al., 2010). Elevated expression of DDX1 mRNA was reported to be a prognostic marker for early recurrence in primary breast cancer (Germain et al., 2010). Recently, it was demonstrated that DDX1 is essential for the solid tumor formation of a human testicular tumor cell line NEC8 in nude mice (Tanaka et al., 2009). In this case, DDX1 directly bound to the -348 and -329 promoter region of the cyclin-D2 gene and enhanced its transcription. Furthermore, siRNA-mediated knockdown of DDX1 resulted in coordinated down-regulation of stem cell-associated genes located in chromosomal region 12p13. Therefore, DDX1 may function as an essential transcriptional activator for the tumorigenic capacity of testicular germ line tumor-derived cells. In agreement, DDX1 promotes the proliferation of JC virus via the transcriptional activation of its viral promoter (Sunden et al., 2007). It was also reported that DDX1 acts as a co-activator to enhance NF-kappaB-mediated transcription (Ishaq et al., 2009). |
Genomic and clinical analyses of 2p24 and 12q13-q14 amplification in alveolar rhabdomyosarcoma: a report from the Children's Oncology Group. |
Barr FG, Duan F, Smith LM, Gustafson D, Pitts M, Hammond S, Gastier-Foster JM. |
Genes Chromosomes Cancer. 2009 Aug;48(8):661-72. |
PMID 19422036 |
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Association of human DEAD box protein DDX1 with a cleavage stimulation factor involved in 3'-end processing of pre-MRNA. |
Bleoo S, Sun X, Hendzel MJ, Rowe JM, Packer M, Godbout R. |
Mol Biol Cell. 2001 Oct;12(10):3046-59. |
PMID 11598190 |
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An RNA helicase, DDX1, interacting with poly(A) RNA and heterogeneous nuclear ribonucleoprotein K. |
Chen HC, Lin WC, Tsay YG, Lee SC, Chang CJ. |
J Biol Chem. 2002 Oct 25;277(43):40403-9. Epub 2002 Aug 14. |
PMID 12183465 |
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The RNA helicase DDX1 is involved in restricted HIV-1 Rev function in human astrocytes. |
Fang J, Acheampong E, Dave R, Wang F, Mukhtar M, Pomerantz RJ. |
Virology. 2005 Jun 5;336(2):299-307. |
PMID 15892970 |
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DEAD box 1: a novel and independent prognostic marker for early recurrence in breast cancer. |
Germain DR, Graham K, Glubrecht DD, Hugh JC, Mackey JR, Godbout R. |
Breast Cancer Res Treat. 2010 May 25. [Epub ahead of print] |
PMID 20499159 |
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Overexpression of a DEAD box protein (DDX1) in neuroblastoma and retinoblastoma cell lines. |
Godbout R, Packer M, Bie W. |
J Biol Chem. 1998 Aug 14;273(33):21161-8. |
PMID 9694872 |
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Amplification of a DEAD box protein gene in retinoblastoma cell lines. |
Godbout R, Squire J. |
Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7578-82. |
PMID 7689221 |
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Loss-of-function screening by randomized intracellular antibodies: identification of hnRNP-K as a potential target for metastasis. |
Inoue A, Sawata SY, Taira K, Wadhwa R. |
Proc Natl Acad Sci U S A. 2007 May 22;104(21):8983-8. Epub 2007 May 4. |
PMID 17483488 |
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The DEAD-box RNA helicase DDX1 interacts with RelA and enhances nuclear factor kappaB-mediated transcription. |
Ishaq M, Ma L, Wu X, Mu Y, Pan J, Hu J, Hu T, Fu Q, Guo D. |
J Cell Biochem. 2009 Feb 1;106(2):296-305. |
PMID 19058135 |
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A role for DEAD box 1 at DNA double-strand breaks. |
Li L, Monckton EA, Godbout R. |
Mol Cell Biol. 2008 Oct;28(20):6413-25. Epub 2008 Aug 18. |
PMID 18710941 |
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Birth of the D-E-A-D box. |
Linder P, Lasko PF, Ashburner M, Leroy P, Nielsen PJ, Nishi K, Schnier J, Slonimski PP. |
Nature. 1989 Jan 12;337(6203):121-2. |
PMID 2563148 |
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Gain of MYCN region in a Wilms tumor-derived xenotransplanted cell line. |
Noguera R, Villamon E, Berbegall A, Machado I, Giner F, Tadeo I, Navarro S, Llombart-Bosch A. |
Diagn Mol Pathol. 2010 Mar;19(1):33-9. |
PMID 20186010 |
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DEAD-box proteins: the driving forces behind RNA metabolism. |
Rocak S, Linder P. |
Nat Rev Mol Cell Biol. 2004 Mar;5(3):232-41. (REVIEW) |
PMID 14991003 |
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DDX1 promotes proliferation of the JC virus through transactivation of its promoter. |
Sunden Y, Semba S, Suzuki T, Okada Y, Orba Y, Nagashima K, Umemura T, Sawa H. |
Microbiol Immunol. 2007;51(3):339-47. |
PMID 17380054 |
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DDX1 is required for testicular tumorigenesis, partially through the transcriptional activation of 12p stem cell genes. |
Tanaka K, Okamoto S, Ishikawa Y, Tamura H, Hara T. |
Oncogene. 2009 May 28;28(21):2142-51. Epub 2009 Apr 27. |
PMID 19398953 |
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